Nitric oxide donor-induced apoptosis in smooth muscle cells is modulated by protein kinase C and protein kinase A.
We have demonstrated previously that exogenously applied nitric oxide (NO) redox species induced apoptosis in smooth muscle cells. The present studies were undertaken to characterize further the potential role of protein kinase C and protein kinase A in the regulation of S-nitroso-N-acetylpenicillamine-induced apoptosis in smooth muscle cells. S-nitroso-N-acetylpenicillamine-induced apoptosis was prevented by the protein kinase C inhibitors, calphostin C and H-7, and was potentiated by protein kinase C activator, phorbol 12-myristate 13-acetate (PMA). Furthermore, S-nitroso-N-acetylpenicillamine prolonged membrane translocation of protein kinase C-epsilon. The membrane permeable analogue, dibutyryl-cAMP (Db-cAMP), potentiated S-nitroso-N-acetylpenicillamine-induced apoptosis, whereas the selective protein kinase A competitive inhibitor, Rp-cAMP, prevented S-nitroso-N-acetylpenicillamine-induced apoptosis. These results indicate that both protein kinase C and protein kinase A are involved in S-nitroso-N-acetylpenicillamine-induced apoptosis in smooth muscle cells.
Nishio
E
E
Department of Pharmacology, National Defense Medical College, Saitama, Tokorozawa, Japan.
Watanabe
Y
Y
D000818:Animals; D001011:Aorta / Q000187:drug effects; D017209:Apoptosis / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits; D026423:S-Nitroso-N-Acetylpenicillamine; D014665:Vasodilator Agents / Q000494:pharmacology
D008565:Membrane Proteins; D014665:Vasodilator Agents; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010396:Penicillamine